Publications by authors named "Christine Fehlner-Gardiner"

27 Publications

  • Page 1 of 1

Evidence of Arctic Fox Survival following Exposure to Rabies Virus.

J Wildl Dis 2021 Nov 23. Epub 2021 Nov 23.

US Department of Agriculture, National Wildlife Research Center, 4101 Laporte Avenue, Fort Collins, Colorado 80521, USA.

The arctic fox variant of the rabies virus (RABV) is enzootic in the circumpolar north. Reports of abortive RABV exposures motivated a retrospective analysis of sera from 41 arctic foxes captured at Karrak Lake in Nunavut, Canada, during 2011-2015. Estimated RABV antibody prevalence among foxes was 14% (95% confidence interval, 7-28%).
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http://dx.doi.org/10.7589/JWD-D-21-00071DOI Listing
November 2021

Ecology of Arctic rabies: 60 years of disease surveillance in the warming climate of northern Canada.

Zoonoses Public Health 2021 09 13;68(6):601-608. Epub 2021 May 13.

Groupe de Recherche en Épidémiologie des Zoonoses et Santé Publique, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada.

Rabies occurs throughout the Arctic, representing an ongoing public health concern for residents of northern communities. The Arctic fox (Vulpes lagopus) is the main reservoir of the Arctic rabies virus variant, yet little is known about the epidemiology of Arctic rabies, such as the ecological mechanisms driving where and when epizootics in fox populations occur. In this study, we provide the first portrait of the spatio-temporal spread of rabies across northern Canada. We also explore the impact of seasonal and multiannual dynamics in Arctic fox populations and climatic factors on rabies transmission dynamics. We analysed data on rabies cases collected through passive surveillance systems in the Yukon, Northwest Territories, Nunavut, Nunavik and Labrador from 1953 to 2014. In addition, we analysed a large and unique database of trapped foxes tested for rabies in the Northwest Territories and Nunavut from 1974 to 1984 as part of active surveillance studies. Rabies cases occurred in all Arctic regions of Canada and were relatively synchronous among foxes and dogs (Canis familiaris). This study highlights the spread of Arctic rabies virus variant across northern Canada, with contrasting rabies dynamics between different yet connected areas. Population fluctuations of Arctic fox populations could drive rabies transmission dynamics in a complex way across northern Canada. Furthermore, this study suggests different impacts of climate and sea ice cover on the onset of rabies epizootics in northern Canada. These results lay the groundwork for the development of epidemiological models to better predict the spatio-temporal dynamics of rabies occurrence in both wild and domestic carnivores, leading to better estimates of human exposure and transmission risk.
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http://dx.doi.org/10.1111/zph.12848DOI Listing
September 2021

Rabies surveillance in the United States during 2019.

J Am Vet Med Assoc 2021 Jun;258(11):1205-1220

Objective: To provide epidemiological information on animal and human cases of rabies occurring in the United States during 2019 and summaries of 2019 rabies surveillance for Canada and Mexico.

Animals: All animals submitted for laboratory diagnosis of rabies in the United States during 2019.

Procedures: State and territorial public health departments and USDA Wildlife Services provided data on animals submitted for rabies testing in the United States during 2019. Data were analyzed temporally and geographically to assess trends in domestic and wildlife rabies cases.

Results: During 2019, 53 jurisdictions submitted 97,523 animal samples for rabies testing, of which 94,770 (97.2%) had a conclusive (positive or negative) test result. Of these, 4,690 tested positive for rabies, representing a 5.3% decrease from the 4,951 cases reported in 2018. Texas (n = 565 [12.0%]), New York (391 [8.3%]), Virginia (385 [8.2%]), North Carolina (315 [6.7%]), California (276 [5.9%]), and Maryland (269 [5.7%]) together accounted for almost half of all animal rabies cases reported in 2019. Of the total reported rabid animals, 4,305 (91.8%) were wildlife, with raccoons (n = 1,545 [32.9%]), bats (1,387 [29.6%]), skunks (915 [19.5%]), and foxes (361 [7.7%]) as the primary species confirmed with rabies. Rabid cats (n = 245 [5.2%]) and dogs (66 [1.4%]) accounted for > 80% of rabies cases involving domestic animals in 2019. No human rabies cases were reported in 2019.

Conclusions And Clinical Relevance: The overall number of animal rabies cases decreased from 2018 to 2019. Laboratory diagnosis of rabies in animals is critical to ensure that human rabies postexposure prophylaxis is administered judiciously.
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http://dx.doi.org/10.2460/javma.258.11.1205DOI Listing
June 2021

Role of Oral Rabies Vaccines in the Elimination of Dog-Mediated Human Rabies Deaths.

Emerg Infect Dis 2020 12;26(12):1-9

Domestic dogs are responsible for nearly all the »59,000 global human rabies deaths that occur annually. Numerous control measures have been successful at eliminating dog-mediated human rabies deaths in upper-income countries, including dog population management, parenteral dog vaccination programs, access to human rabies vaccines, and education programs for bite prevention and wound treatment. Implementing these techniques in resource-poor settings can be challenging; perhaps the greatest challenge is maintaining adequate herd immunity in free-roaming dog populations. Oral rabies vaccines have been a cornerstone in rabies virus elimination from wildlife populations; however, oral vaccines have never been effectively used to control dog-mediated rabies. Here, we convey the perspectives of the World Organisation for Animal Health Rabies Reference Laboratory Directors, the World Organisation for Animal Health expert committee on dog rabies control, and World Health Organization regarding the role of oral vaccines for dogs. We also issue recommendations for overcoming hesitations to expedited field use of appropriate oral vaccines.
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http://dx.doi.org/10.3201/eid2612.201266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706920PMC
December 2020

A long-distance translocation initiated an outbreak of raccoon rabies in Hamilton, Ontario, Canada.

PLoS Negl Trop Dis 2020 03 25;14(3):e0008113. Epub 2020 Mar 25.

National Reference Laboratory for Rabies, Ottawa Laboratory-Fallowfield, Canadian Food Inspection Agency, Ottawa, Ontario, Canada.

Despite proactive measures to prevent raccoon rabies entering Canada from the United States, several incursions of this disease have occurred. The largest outbreak, first reported in December 2015 in the city of Hamilton, Ontario, has resulted in the reporting of 449 animal cases as of December 31, 2018. Initial phylogenetic studies on the index case suggested that this outbreak was not due to local cross-border spread from the Niagara region of the United States where raccoon rabies has persisted for several years. Phylogenetic analysis of whole genome sequences of a viral collection from the Hamilton area and several US states indicates that a long-distance translocation of a diseased animal from southeastern New York State was responsible for this incursion. The role of the skunk as a potential secondary host supporting persistence and / or spread of the virus is also examined.
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http://dx.doi.org/10.1371/journal.pntd.0008113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135350PMC
March 2020

Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies.

Trop Med Infect Dis 2020 Jan 18;5(1). Epub 2020 Jan 18.

Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, 17493 Greifswald-Insel Riems, Germany.

As a neglected zoonotic disease, rabies causes approximately 5.9 × 10 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.
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http://dx.doi.org/10.3390/tropicalmed5010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157750PMC
January 2020

Population- and Variant-Based Genome Analyses of Viruses from Vaccine-Derived Rabies Cases Demonstrate Product Specific Clusters and Unique Patterns.

Viruses 2020 01 17;12(1). Epub 2020 Jan 17.

Department of Virology, National Veterinary Research Institute, 24-100 Puławy, Poland.

Rabies in wildlife has been successfully controlled in parts of Europe and North America using oral rabies vaccination, i.e., the distribution of baits containing live-attenuated virus strains. Occasionally, these vaccines caused vaccine virus-induced rabies cases. To elucidate the mechanisms of genetic selection and the effect of viral populations on these rabies cases, a next generation sequencing approach as well as comprehensive data analyses of the genetic diversity of Street Alabama Dufferin (SAD) and ERA vaccine virus strains and vaccine-induced rabies cases from Canada and several European countries were conducted. As a result, twelve newly generated sets of sequencing data from Canada and Poland were added to a pool of previously investigated samples. While the population-based analysis showed a segregation of viruses of ERA vaccine-induced rabies cases from those of SAD Bern original (SAD Bern)-derived rabies cases, the in-depth variant analysis revealed three distinct combinations of selected variants for the ERA vaccine-induced cases, suggesting the presence of multiple replication-competent haplotypes in the investigated ERA-BHK21 vaccine. Our findings demonstrate the potential of a deep sequencing approach in combination with comprehensive analyses on the consensus, population, and variant level.
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http://dx.doi.org/10.3390/v12010115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020022PMC
January 2020

Public Veterinary Medicine: Public Health: Rabies surveillance in the United States during 2018.

J Am Vet Med Assoc 2020 01;256(2):195-208

Objective: To describe rabies and rabies-related events occurring during 2018 in the United States.

Animals: All animals submitted for laboratory diagnosis of rabies in the United States during 2018.

Procedures: State and territorial public health departments provided data on animals submitted for rabies testing in 2018. Data were analyzed temporally and geographically to assess trends in domestic animal and wildlife rabies cases.

Results: During 2018, 54 jurisdictions reported 4,951 rabid animals to the CDC, representing an 11.2% increase from the 4,454 rabid animals reported in 2017. Texas (n = 695 [14.0%]), Virginia (382 [7.7%]), Pennsylvania (356 [7.2%]), North Carolina (332 [6.7%]), Colorado (328 [6.6%]), and New York (320 [6.5%]) together accounted for almost half of all rabid animals reported in 2018. Of the total reported rabies cases, 4,589 (92.7%) involved wildlife, with bats (n = 1,635 [33.0%]), raccoons (1,499 [30.3%]), skunks (1,004 [20.3%]), and foxes (357 [7.2%]) being the major species. Rabid cats (n = 241 [4.9%]) and dogs (63 [1.3%]) accounted for > 80% of rabid domestic animals reported in 2018. There was a 4.6% increase in the number of samples submitted for testing in 2018, compared with the number submitted in 2017. Three human rabies deaths were reported in 2018, compared with 2 in 2017.

Conclusions And Clinical Relevance: The overall number of animal rabies cases increased from 2017 to 2018. Laboratory diagnosis of rabies in animals is critical to ensure that human rabies postexposure prophylaxis is administered judiciously.
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http://dx.doi.org/10.2460/javma.256.2.195DOI Listing
January 2020

Origins of the arctic fox variant rabies viruses responsible for recent cases of the disease in southern Ontario.

PLoS Negl Trop Dis 2019 09 6;13(9):e0007699. Epub 2019 Sep 6.

National Reference Laboratory for Rabies, Ottawa Laboratory-Fallowfield, Canadian Food Inspection Agency, Ottawa, Ontario.

A subpopulation of the arctic fox lineage of rabies virus has circulated extensively in red fox populations of Ontario, Canada, between the 1960s and 1990s. An intensive wildlife rabies control program, in which field operations were initiated in 1989, resulted in elimination of the disease in eastern Ontario. However in southwestern Ontario, as numbers of rabid foxes declined the proportion of skunks confirmed to be infected with this rabies virus variant increased and concerted control efforts targeting this species were employed to eliminate the disease. Since 2012 no cases due to this viral variant were reported in southwestern Ontario until 2015 when a single case of rabies due to the arctic fox variant was reported in a bovine. Several additional cases have been documented subsequently. Since routine antigenic typing cannot discriminate between the variants which previously circulated in Ontario and those from northern Canada it was unknown whether these recent cases were the result of a new introduction of this variant or a continuation of the previous enzootic. To explore the origins of this new outbreak whole genome sequences of a collection of 128 rabies viruses recovered from Ontario between the 1990s to the present were compared with those representative of variants circulating in the Canadian north. Phylogenetic analysis shows that the variant responsible for current cases in southwestern Ontario has evolved from those variants known to circulate in Ontario previously and is not due to a new introduction from northern regions. Thus despite ongoing passive surveillance the persistence of wildlife rabies went undetected in the study area for almost three years. The apparent adaptation of this rabies virus variant to the skunk host provided the opportunity to explore coding changes in the viral genome which might be associated with this host shift. Several such changes were identified including a subset for which the operation of positive selection was supported. The location of a small number of these amino acid substitutions in or close to protein motifs of functional importance suggests that some of them may have played a role in this host shift.
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http://dx.doi.org/10.1371/journal.pntd.0007699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750613PMC
September 2019

ONRAB® oral rabies vaccine is shed from, but does not persist in, captive mammals.

Vaccine 2019 07 24;37(31):4310-4317. Epub 2019 Jun 24.

Natural Resources DNA Profiling and Forensics Centre, 2140 East Bank Drive, DNA Building, Trent University, Peterborough, Ontario K9J 7B8, Canada. Electronic address:

ONRAB® is a human adenovirus rabies glycoprotein recombinant vaccine developed to control rabies in wildlife. To support licensing and widespread use of the vaccine, safety studies are needed to assess its potential residual impact on wildlife populations. We examined the persistence of the ONRAB® vaccine virus in captive rabies vector and non-target mammals. This research complements work on important rabies vector species (raccoon, striped skunk, and red fox) but also adds to previous findings with the addition of some non-target species (Virginia opossum, Norway rats, and cotton rats) and a prolonged period of post vaccination monitoring (41 days). Animals were directly inoculated orally with the vaccine and vaccine shedding was monitored using quantitative real-time PCR applied to oral and rectal swabs. ONRAB® DNA was detected in both oral and rectal swabs from 6 h to 3 days post-inoculation in most animals, followed by a resurgence of shedding between days 17 and 34 in some species. Overall, the duration over which ONRAB® DNA was detectable was shorter for non-target mammals, and by day 41, no animal had detectable DNA in either oral or rectal swabs. All target species, as well as cotton rats and laboratory-bred Norway rats, developed robust humoral immune responses as measured by competitive ELISA, with all individuals being seropositive at day 31. Similarly, opossums showed good response (89% seropositive; 8/9), whereas only one of nine wild caught Norway rats was seropositive at day 31. These results support findings of other safety studies suggesting that ONRAB® does not persist in vector and non-target mammals exposed to the vaccine. As such, we interpret these data to reflect a low risk of adverse effects to wild populations following distribution of ONRAB® to control sylvatic rabies.
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http://dx.doi.org/10.1016/j.vaccine.2019.06.046DOI Listing
July 2019

Avoiding preventable deaths: The scourge of counterfeit rabies vaccines.

Vaccine 2019 04 25;37(17):2285-2287. Epub 2019 Mar 25.

Animal and Plant Health Agency, WHO Collaborating Centre for Characterisation of Rabies and Rabies-Related Viruses, OIE Reference Laboratory for Rabies, Weybridge, UK; Institute of Infection & Global Health, University of Liverpool, Liverpool, UK; St. George's Hospital Medical School, Institute for Infection and Immunity, University of London, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.vaccine.2019.03.037DOI Listing
April 2019

In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

Vaccine 2019 08 10;37(33):4758-4765. Epub 2018 Feb 10.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald, Germany. Electronic address:

Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection.
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http://dx.doi.org/10.1016/j.vaccine.2018.01.083DOI Listing
August 2019

Incorporating Direct Rapid Immunohistochemical Testing into Large-Scale Wildlife Rabies Surveillance.

Trop Med Infect Dis 2017 Jun 30;2(3). Epub 2017 Jun 30.

Ontario Ministry of Natural Resources and Forestry, Wildlife Research and Monitoring Section, Peterborough, ON K9L 0G2, Canada.

Following an incursion of the mid-Atlantic raccoon variant of the rabies virus into southern Ontario, Canada, in late 2015, the direct rapid immunohistochemical test for rabies (dRIT) was employed on a large scale to establish the outbreak perimeter and to diagnose specific cases to inform rabies control management actions. In a 17-month period, 5800 wildlife carcasses were tested using the dRIT, of which 307 were identified as rabid. When compared with the gold standard fluorescent antibody test (FAT), the dRIT was found to have a sensitivity of 100% and a specificity of 98.2%. Positive and negative test agreement was shown to be 98.3% and 99.1%, respectively, with an overall test agreement of 98.8%. The average cost to test a sample was $3.13 CAD for materials, and hands-on technical time to complete the test is estimated at 0.55 h. The dRIT procedure was found to be accurate, fast, inexpensive, easy to learn and perform, and an excellent tool for monitoring the progression of a wildlife rabies incursion.
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http://dx.doi.org/10.3390/tropicalmed2030021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082085PMC
June 2017

Antigenic characterisation of lyssaviruses in South Africa.

Onderstepoort J Vet Res 2014 Sep 11;81(1). Epub 2014 Sep 11.

Agriculture Research Council-Onderstepoort Veterinary Research, University of Pretoria.

There are at least six Lyssavirus species that have been isolated in Africa, which include classical rabies virus, Lagos bat virus, Mokola virus, Duvenhage virus, Shimoni bat virus and Ikoma lyssavirus. In this retrospective study, an analysis of the antigenic reactivity patterns of lyssaviruses in South Africa against a panel of 15 anti-nucleoprotein monoclonal antibodies was undertaken. A total of 624 brain specimens, collected between 2005 and 2009, confirmed as containing lyssavirus antigen by direct fluorescent antibody test, were subjected to antigenic differentiation. The lyssaviruses were differentiated into two species, namely rabies virus (99.5%) and Mokola virus (0.5%). Furthermore, rabies virus was further delineated into two common rabies biotypes in South Africa: canid and mongoose. Initially, it was found that the canid rabies biotype had two reactivity patterns; differential staining was observed with just one monoclonal antibody. This difference was likely to have been an artefact related to sample quality, as passage in cell culture restored staining. Mongoose rabies viruses were more heterogeneous, with seven antigenic reactivity patterns detected. Although Mokola viruses were identified in this study, prevalence and reservoir host species are yet to be established. These data demonstrate the usefulness of monoclonal antibody typing panels in lyssavirus surveillance with reference to emergence of new species or spread of rabies biotypes to new geographic zones.
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http://dx.doi.org/10.4102/ojvr.v81i1.711DOI Listing
September 2014

Characterizing rabies epidemiology in remote Inuit communities in Québec, Canada: a "One Health" approach.

Ecohealth 2014 Sep 19;11(3):343-55. Epub 2014 Mar 19.

Groupe international vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, 3200 Sicotte, C.P. 5000, Saint-Hyacinthe, QC, J2S 7C6, Canada,

Rabies is endemic throughout arctic areas including the region of Nunavik, situated north of the 55th parallel of Québec, Canada, and raises public health concerns. The aim of this paper is to provide a descriptive overview of the temporal and regional distributions of three important components of arctic rabies in Nunavik from 1999 to 2012, following a "One Health" approach: animal rabies tests and confirmed cases, dog vaccination, and human consultations for potential rabies exposures. Forty-four cases of rabies, involving mainly arctic and red foxes, were confirmed in animals during this period. The mean number of dogs vaccinated per 1,000 inhabitants was highly variable and lower in the Hudson region than the Ungava region. 112 consultations for potential rabies exposure were analyzed, of which 24 were exposure to a laboratory confirmed rabid animal. Children less than 10 years of age were the age group most commonly exposed. The median time between potential exposure and administration of the first post-exposure prophylaxis dose was four days. This study confirms that the risk of human exposure to rabid animals in Nunavik is present and underlines the need to follow a "One Health" approach to prevent rabies in humans in similar contexts worldwide.
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http://dx.doi.org/10.1007/s10393-014-0923-1DOI Listing
September 2014

Oral rabies vaccination in raccoons: comparison of ONRAB® and RABORAL V-RG® vaccine-bait field performance in Québec, Canada and Vermont, USA.

J Wildl Dis 2013 Jan;49(1):190-3

Ministère des Ressources naturelles et de la Faune, Direction générale de l'expertise sur la faune et ses habitats, Direction de la biodiversité et des maladies de la faune, 880 chemin Sainte-Foy, 2e étage, Québec, Québec G1S 4X4, Canada.

The control of rabies in raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) in North America has been conducted mainly through aerial distribution of oral vaccine-baits. The effectiveness of the vaccine-bait used is therefore of prime importance for disease eradication. In a previous field comparison between the ONRAB(®) bait in the province of New Brunswick, Canada, and RABORAL V-RG(®) bait in the state of Maine, USA, the ONRAB bait produced a higher percentage of antibody-positive raccoons under nearly identical bait distribution for the two vaccines. The main objective of the present study was to conduct a similar cross-border comparison of these two vaccine-baits using raccoon sera collected during post-oral rabies vaccination monitoring in Québec, Canada, and Vermont, USA, where ONRAB and V-RG, respectively, were distributed aerially at a targeted density of 150 baits/km(2). A comparison of the equivalency of two serologic tests used in Canada and the USA was also conducted using sera from raccoons and striped skunks. Rabies virus neutralization assay (USA) yielded similar results to the competitive enzyme-linked immunosorbent assay (Canada), with agreement between the two tests of 92% for raccoon sera and 96% for skunk sera. With both assays, the percentage of antibody-positive raccoons was greater with ONRAB (51%, n=265) than with V-RG (38%, n=66). These new results support the conclusion from the previous study, that ONRAB vaccine-baits may be more effective for the control of rabies in raccoons.
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http://dx.doi.org/10.7589/2011-11-342DOI Listing
January 2013

Oral rabies vaccination of raccoons and striped skunks with ONRAB® baits: multiple factors influence field immunogenicity.

J Wildl Dis 2012 Oct;48(4):979-90

Ministère des Ressources Naturelles et de la Faune, Direction Générale de l'Expertise sur la Faune et ses Habitats, Direction de la Biodiversité et des Maladies de la Faune, 880 Chemin Sainte-Foy, 2 étage, Québec, Québec G1S 4X4, Canada.

Multiple control methods have been used in North America to manage the spread of rabies caused by the raccoon (Procyon lotor) rabies virus variant (RRVV). Recently, oral vaccination with ONRAB(®) vaccine baits, which contain an adenovirus rabies glycoprotein recombinant, has been made available as an additional tool for rabies control. Our objectives were to estimate rabies antibody prevalence in wild-caught raccoons and striped skunks (Mephitis mephitis), and identify factors influencing the probability of being antibody positive at the individual level in these species, following oral rabies vaccination (ORV) campaigns in which ONRAB was distributed aerially in 2007-2009 in southern Québec, Canada. Following the aerial distribution of 43-155 ONRAB baits/km(2), the annual percentages of antibody-positive raccoons and skunks varied between 35% and 56% and 11% and 17%, respectively. In raccoons, the probability of being antibody positive was positively associated with age and density of ONRAB distributed, and influenced by the number of previous ORV campaigns conducted. Conversely, this probability was negatively associated with estimated abundance of raccoons in the trapping cell and proportion of residential areas near the raccoon capture location. None of the variables examined explained variation in the probability of being antibody positive in skunks. Our results indicate that the ONRAB density applied during ORV campaigns should be adjusted to account for variations in raccoon population density and presence of residential areas to increase the likelihood of creating an effective immunological barrier against RRVV. The high percentage of juvenile raccoons (annual mean =45 ± 3 [SE]%) and skunks (66 ± 2%) captured during post-ORV monitoring suggests that ORV campaigns should be conducted at least annually to account for the recruitment of naïve individuals into the populations. In Québec, the increasing use of ONRAB coincided with the elimination of rabies caused by RRVV. Nonetheless, our results indicate that improvements to this vaccine bait and/or the distribution techniques are required to increase its efficacy, especially in striped skunks.
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http://dx.doi.org/10.7589/2011-12-316DOI Listing
October 2012

Comparing ONRAB® AND RABORAL V-RG® oral rabies vaccine field performance in raccoons and striped skunks, New Brunswick, Canada, and Maine, USA.

J Wildl Dis 2012 Jan;48(1):157-67

Centre of Expertise for Rabies, Canadian Food Inspection Agency, 3851 Fallowfield Rd., PO Box 11300, Station H, Ottawa, Ontario K2H 8P9, Canada.

Control of rabies in mesocarnivore reservoirs through oral rabies vaccination (ORV) requires an effective vaccine bait. Oral rabies vaccine performance in the field may be affected by a variety of factors, including vaccine bait density and distribution pattern, habitat, target species population density, and the availability of competing foods. A field study in which these covariates were restricted as much as possible was conducted along the international border of the state of Maine (ME), USA, and the province of New Brunswick (NB), Canada, to compare the performance of two oral rabies vaccines in raccoons (Procyon lotor) and striped skunks (Mephitis mephitis). RABORAL V-RG(®) (vaccinia-rabies glycoprotein recombinant oral vaccine in fishmeal-coated sachet) or ONRAB(®) (adenovirus-rabies glycoprotein recombinant oral vaccine in Ultralite bait matrix) were distributed in ME and NB, respectively, by fixed-wing aircraft at a density of 75 baits/km(2) along parallel flight lines spaced 1.0 km apart. Sera were collected from live-trapped raccoons and skunks 5-7 wk post-ORV and assayed to determine antibody prevalence in each area. Duplicate serum samples were provided blind to two different laboratories for analyses by rabies virus serum neutralization assays (at both laboratories) and a competitive enzyme-linked immunosorbent assay (at one laboratory). There was no significant difference in the proportion of antibody-positive animals determined by the three serologic methods, nor was there a significant difference between ONRAB and RABORAL V-RG in the proportion of antibody-positive striped skunks observed post-ORV. In contrast, the proportion of antibody-positive raccoons was significantly higher in the ONRAB- versus the RABORAL V-RG-baited areas (74% vs. 30%; χ(2)=89.977, df=5, P<0.0001). These data support that ONRAB may serve as an effective tool for raccoon rabies control.
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http://dx.doi.org/10.7589/0090-3558-48.1.157DOI Listing
January 2012

Characterization of a panel of anti-phosphoprotein monoclonal antibodies generated against the raccoon strain of rabies virus.

Virus Res 2010 Sep 23;152(1-2):126-36. Epub 2010 Jun 23.

Centre of Expertise for Rabies, Ottawa Laboratory (Fallowfield), Canadian Food Inspection Agency, 3851 Fallowfield Rd., Ottawa, Ontario, Canada.

The generation of a new panel of 32 monoclonal antibodies (MAbs) reactive with the P protein of the raccoon strain of rabies virus is described. Through a series of analyses employing competitive ELISA and immunoblotting, these MAbs were classified into eight groups, each defining an antigenic site, thereby increasing the number of sites now recognized along the length of the P protein. Studies on MAb reactivity with a collection of diverse lyssaviruses identified sites that were highly conserved, moderately conserved and highly variable. Several groups of MAbs were highly specific for the raccoon rabies virus (RRV) strain and may be useful for inclusion into panels used for antigenic typing of rabies viruses. The utility of these MAbs to detect truncated versions of the P product may facilitate more fundamental studies on the function of this rabies virus protein.
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http://dx.doi.org/10.1016/j.virusres.2010.06.014DOI Listing
September 2010

Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans.

PLoS Negl Trop Dis 2009 Nov 3;3(11):e542. Epub 2009 Nov 3.

WHO Collaborating Centre for Rabies Surveillance and Research, Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Wusterhausen, Germany.

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans.
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http://dx.doi.org/10.1371/journal.pntd.0000542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765635PMC
November 2009

Lyssaviruses: current trends.

Adv Virus Res 2008 ;71:207-50

Centre of Expertise for Rabies, Ottawa Laboratory (Fallowfield), Canadian Food Inspection Agency, Ottawa, ON, Canada.

Various technological developments have revitalized the approaches employed to study the disease of rabies. In particular, reverse genetics has facilitated the generation of novel viruses used to improve our understanding of the fundamental aspects of rabies virus (RABV) biology and pathogenicity and yielded novel constructs potentially useful as vaccines against rabies and other diseases. Other techniques such as high throughput methods to examine the impact of rabies virus infection on host cell gene expression and two hybrid systems to explore detailed protein-protein interactions also contribute substantially to our understanding of virus-host interactions. This review summarizes much of the increased knowledge about rabies that has resulted from such studies but acknowledges that this is still insufficient to allow rational attempts at curing those who present with clinical disease.
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http://dx.doi.org/10.1016/S0065-3527(08)00005-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119311PMC
August 2008

Laboratory diagnosis of rabies in Canada for calendar year 2006.

Can Vet J 2008 Apr;49(4):359-61

Canadian Food Inspection Agency, Ottawa Laboratory Fallowfield, Ottawa, Ontario.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275337PMC
April 2008

Era vaccine-derived cases of rabies in wildlife and domestic animals in Ontario, Canada, 1989-2004.

J Wildl Dis 2008 Jan;44(1):71-85

Centre of Expertise for Rabies, Ottawa Laboratory-Fallowfield, Canadian Food Inspection Agency, 3851 Fallowfield Road, Ottawa, Ontario K2H 8P9, Canada.

A vaccination program for the control of terrestrial rabies in the province of Ontario, Canada, began in 1989. During the period between 1989 and 2004, over 13 million baits containing the live, attenuated rabies virus ERA-BHK21 were distributed across the province, with the aim of immunizing foxes by the oral route. Animals recovered from bait distribution areas were assayed by fluorescent antibody test for rabies virus infection. Immunoreactivity with a panel of monoclonal antibodies that discriminate between ERA and rabies virus variants known to circulate in Ontario, and molecular genetic analyses were used to identify animals infected with ERA. Nine cases of ERA variant rabies were identified over the 16-yr period of study; these did not appear to be stratified by species, year of discovery, or location of capture. The ERA-positive animals were found across the province in eight counties, all of which had been baited in the year of case discovery. The nine ERA-positive cases included four red foxes (Vulpes vulpes), two raccoons (Procyon lotor), two striped skunks (Mephitis mephitis), and one bovine calf (Bos taurus). Molecular phylogenetic analyses of the partial N gene sequences generated from these isolates indicated that these nine cases were due to infection with the ERA variant. The glycoprotein sequences were predicted from G gene sequencing of all nine field isolates and two laboratory stock ERA viruses. This revealed some heterogeneity at residue 120 (either arginine or histidine) in both field and laboratory stocks as well as a few other mutations in field isolates. The significance of this heterogeneity remains unclear. Our data demonstrate that the ERA vaccine distributed in Ontario carried residual pathogenicity; however, there does not appear to be any evidence of ERA establishment in wildlife populations over the 16-yr period. These results are consistent with previous reports of the rare detection of ERA vaccine-induced rabies and with laboratory studies of ERA pathogenicity.
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http://dx.doi.org/10.7589/0090-3558-44.1.71DOI Listing
January 2008

Cloning and characterization of the Burkholderia vietnamiensis norM gene encoding a multi-drug efflux protein.

FEMS Microbiol Lett 2002 Oct;215(2):279-83

Department of Microbiology and Immunology, University of Western Ontario, London, Canada N6A 5C1.

Polymyxin B-sensitive mutants in Burkholderia vietnamiensis (Burkholderia cepacia genomovar V) were generated with a mini-Tn5 encoding tetracycline resistance. One of the transposon mutants had an insertion in the norM gene encoding a multi-drug efflux protein. Expression of B. vietnamiensis norM in an Escherichia coli acrAB deletion mutant complemented its norfloxacin hypersensitivity, indicating that the protein functions in drug efflux. However, no effect on antibiotic sensitivity other than sensitivity to polymyxin B was observed in the B. vietnamiensis norM mutant. We demonstrate that increased polymyxin sensitivity in B. vietnamiensis was associated with the presence of tetracycline in the growth medium, a phenotype that was partially suppressed by expression of the norM gene.
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http://dx.doi.org/10.1111/j.1574-6968.2002.tb11403.xDOI Listing
October 2002

Identification of a general secretory pathway in a human isolate of Burkholderia vietnamiensis (formerly B. cepacia complex genomovar V) that is required for the secretion of hemolysin and phospholipase C activities.

Microb Pathog 2002 May;32(5):249-54

Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.

Members of the Burkholderia cepacia complex can secrete proteases, lipases, and hemolysins. We report in this study the identification of a general secretory pathway present in a B. vietnamiensis (formerly genomovar V) clinical isolate, which is required for the efficient secretion of phospholipase C and hemolysin activities. Southern blot hybridization experiments revealed that this general secretion pathway is highly conserved among the different genomovars of the B. cepacia complex and is homologous to a similar system described in B. pseudomallei. We also show that this pathway appears not to be necessary for intracellular survival of B. vietnamiensis within Acanthamoeba polyphaga.
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http://dx.doi.org/10.1006/mpat.2002.0503DOI Listing
May 2002

Molecular basis defining human Chlamydia trachomatis tissue tropism. A possible role for tryptophan synthase.

J Biol Chem 2002 Jul 13;277(30):26893-903. Epub 2002 May 13.

Department of Medical Microbiology, University of Manitoba and National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba R3E 0W3, Canada.

Here we report the cloning and sequencing of a region of the chlamydiae chromosome termed the "plasticity zone" from all the human serovars of C. trachomatis containing the tryptophan biosynthesis genes. Our results show that this region contains orthologues of the tryptophan repressor as well as the alpha and beta subunits of tryptophan synthase. Results from reverse transcription-PCR and Western blot analyses indicate that the trpBA genes are transcribed, and protein products are expressed. The TrpB sequences from all serovars are highly conserved. In comparison with other tryptophan synthase beta subunits, the chlamydial TrpB subunit retains all conserved amino acid residues required for beta reaction activity. In contrast, the chlamydial TrpA sequences display numerous mutations, which distinguish them from TrpA sequences of all other prokaryotes. All ocular serovars contain a deletion mutation resulting in a truncated TrpA protein, which lacks alpha reaction activity. The TrpA protein from the genital serovars retains conserved amino acids required for catalysis but has mutated several active site residues involved in substrate binding. Complementation analysis in Escherichia coli strains, with defined mutations in tryptophan biosynthesis, and in vitro enzyme activity data, with cloned TrpB and TrpA proteins, indicate these mutations result in a TrpA protein that is unable to utilize indole glycerol 3-phosphate as substrate. In contrast, the chlamydial TrpB protein can carry out the beta reaction, which catalyzes the formation of tryptophan from indole and serine. The activity of the chlamydial Trp B protein differs from that of the well characterized E. coli and Salmonella TrpBs in displaying an absolute requirement for full-length TrpA. Taken together our data indicate that genital, but not ocular, serovars are capable of utilizing exogenous indole for the biosynthesis of tryptophan.
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http://dx.doi.org/10.1074/jbc.M203937200DOI Listing
July 2002
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